Effect of adrenomedullin gene delivery on insulin resistance in type 2 diabetic rats

Henein, Hoda Y.; Younan, Sandra; Rashed, Leila A.; Fakhry, Amy

doi:10.1016/j.jare.2010.08.002

Cited by 3 publications

(2 citation statements)

References 55 publications

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“…However, the effect of ADM on hyperglycemia and IR could be clarified by ADM‐mediated increased glucose utilization via upregulation of glucose transporter 4 (GLUT‐4) in the membranes of skeletal muscles via the Akt pathway. [ 39 ] Previous reports revealed that the inhibition of insulin signaling on skeletal muscle membranes was sufficient enough to cause IR. [ 40 ] The antioxidant effect of ADM might be a reasonable mechanism for the improvement of IR as was documented in our study.…”

Section: Discussionmentioning

confidence: 99%

Potential effect of adrenomedullin on metabolic and endocrinal dysfunctions in the experimentally induced polycystic ovary: Targeting implication of endoplasmic reticulum stress

El-Saka

Barhoma

Ibrahim

et al. 2021

J Biochem & Molecular Tox

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This study investigated the potential effect of adrenomedullin (ADM) on metabolic and endocrinal dysfunctions in experimentally induced polycystic ovary. Twenty‐four female Wistar rats were allocated into three groups: control; polycystic ovary syndrome (PCOS) in which PCOS was induced by letrozole, orally in a dose of 1 mg/kg once daily for 3 weeks; and ADM group in which ADM was injected intraperitonally in a dose of 3.5/μg/twice daily for 4 weeks. At the end of the experimental period, the serum sex hormone profile, ADM, fasting glucose, insulin, homeostatic model assessment of insulin resistance, and lipid parameters were determined. Ovarian tissue homogenates were used to determine malondialdehyde, total antioxidant capacity, glutathione peroxidase activity, tumor necrosis factor α, interleukin 6, B cell lymphoma‐2 (Bcl‐2), and Bcl‐2 associated X protein. The profibrotic growth factors, including transforming growth factor β1 and connective tissue growth factor, were determined; and also, the relative gene expression of endoplasmic reticulum (ER) stress, including (Xbox‐binding protein‐1 [XBP‐1], activating transcription factor 6 [ATF6], and homologous protein [CHOP]), serine/threonine kinase 1 (Akt1), phosphatidylinositol 3‐kinase (PI3K), and peroxisome proliferator‐activated receptor γ (PPAR‐γ) were determined. Finally, histopathological analysis of the ovaries was evaluated. PCOS group exhibited increased ER stress, suppressing of PI3K/Akt1 and PPAR‐γ pathways, imbalance of sex hormonal profile, hyperglycemia, insulin resistance, dyslipidemia, increased profibrotic factors, and abnormal ovarian histopathological picture, while ADM treatment alleviated these disturbances occurring in the PCOS model. We concluded that ADM mitigated PCOS via attenuating the ER stress, in addition to activation of PI3K/Akt1 and PPAR‐γ pathways, its antioxidant, anti‐inflammatory, antiapoptotic, and antifibrotic properties.

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Section: Discussionmentioning

confidence: 99%

Potential effect of adrenomedullin on metabolic and endocrinal dysfunctions in the experimentally induced polycystic ovary: Targeting implication of endoplasmic reticulum stress

El-Saka

Barhoma

Ibrahim

et al. 2021

J Biochem & Molecular Tox

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show abstract

“…Total cholesterol was determined by a quantitative colorimetric method (EnzyChrom ECCH-100, BioAssay Systems, Hayward, CA), according to the kit instructions [54]. This assay has a lower detection limit of 5 mg/dl.…”

Section: Methodsmentioning

confidence: 99%

Chronic social isolation in the prairie vole induces endothelial dysfunction: implications for depression and cardiovascular disease

Peuler

Scotti

Phelps

et al. 2012

Physiology & Behavior

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Humans with depression show impaired endothelium-dependent vasodilation, one recent demonstration of which was in the form of a reduced acetylcholine (ACh)-induced relaxation of adrenergically-precontracted small arteries biopsied from older depressed patients. Results from such uses of ACh in general have been validated as the most predictive marker of endothelium-related cardiovascular diseases. Accordingly, we examined vascular reactivity to ACh in the socially isolated prairie vole, a new animal model relevant to human depression and cardiovascular disease. Thoracic aortas were carefully dissected from female prairie voles after one month of social isolation (versus pairing with a sibling). Only aortas that contracted to the adrenergic agent phenylephrine (PE) and then relaxed to ACh were evaluated. Among those, ACh-induced relaxations were significantly reduced by social isolation (p<0.05), with maximum relaxation reaching only 30% (of PE-induced precontraction) compared to 47% in aortas from paired (control) animals. Experimental removal of the endothelium from an additional set of aortic tissues abolished all ACh relaxations including that difference. In these same tissues, maximally-effective concentrations of the nitric oxide-donor nitroprusside still completely relaxed all PE-induced precontraction of the endothelial-free smooth muscle, and to the same degree in tissues from isolated versus paired animals. Finally, in the absence of PE-induced precontraction ACh did not relax but rather contracted aortic tissues, and to a significantly greater extent in tissues from socially isolated animals if the endothelium was intact (p<0.05). Thus, social isolation in the prairie vole may 1) impair normal release of protective anti-atherosclerotic factors like nitric oxide from the vascular endothelium (without altering the inherent responsiveness of the vascular smooth muscle to such factors) and 2) cause the endothelium to release contracting factors. To our knowledge this is the first demonstration of this phenomenon in an animal model of depression induced solely by social isolation. These findings have implications for understanding mechanisms involved in depression and cardiovascular disease.

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An atlas of G-protein coupled receptor expression and function in human subcutaneous adipose tissue

Amisten

Neville

Hawkes

et al. 2015

Pharmacology & Therapeutics

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Effect of adrenomedullin gene delivery on insulin resistance in type 2 diabetic rats

Cited by 3 publications

References 55 publications

Potential effect of adrenomedullin on metabolic and endocrinal dysfunctions in the experimentally induced polycystic ovary: Targeting implication of endoplasmic reticulum stress

Potential effect of adrenomedullin on metabolic and endocrinal dysfunctions in the experimentally induced polycystic ovary: Targeting implication of endoplasmic reticulum stress

Chronic social isolation in the prairie vole induces endothelial dysfunction: implications for depression and cardiovascular disease

An atlas of G-protein coupled receptor expression and function in human subcutaneous adipose tissue

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